A Comparison of 3 Regimens to Prevent Nevirapine Resistance Mutations in HIV-Infected Pregnant Women Receiving a Single Intrapartum Dose of Nevirapine

The administration of single-dose (SD) nevirapine (NVP) at delivery to human immunodeficiency virus (HIV)–infected pregnant women and their newborns after antenatal zidovudine therapy decreases the risk of perinatal mother-to-child transmission (MTCT) of HIV infection to 1.9% among formula-fed infants [1]. However, SD-NVP commonly leads to the emergence of NVP-resistant virus in the mother, with ≥85% of mothers having resistant virus detectable using sensitive assays [2, 3]. The resistant virus becomes undetectable in most women 12–24 months after delivery but may persist at a low frequency in plasma or lymphocytes [2, 4–6]. Furthermore, receipt of SD-NVP increases the risk of failure of subsequent NVP-containing therapy, particularly if initiated within the first 6–24 months after receiving SD-NVP [7–13]. The Treatment Options Preservation Study (TOPS) study demonstrated that the addition of a short (4- or 7-day) postpartum course (“tail”) of zidovudine plus lamivudine after SD-NVP reduced the incidence of NVP resistance mutations from 59% to 12% and 7.3%, respectively, when measured by consensus sequencing, an insensitive assay [14]. Other effective tails include 3 days of zidovudine and lamivudine (1.4% NVP resistance by sequencing) [15], a single dose of tenofovir and emtricitabine (12% by sequencing and 19% by the sensitive oligonucleotide ligation assay [OLA]) [16, 17] and 7 days of tenofovir and emtricitabine (none by sequencing) [18, 19]. Extending the duration of the tail may increase its effectiveness, with 1 month of zidovudine and didanosine resulting in an incidence of resistance of 0% by sequencing and 1.8% by OLA [20]. Use of a zidovudine and lamivudine tail can also result in lamivudine resistance, particularly among women who receive prenatal lamivudine [15]. The World Health Organization recommends a 7-day tail of zidovudine plus lamivudine for women who receive SD-NVP [21]. The plasma half-life of NVP after SD-NVP is long, and plasma concentrations persist at subtherapeutic concentrations for 3–4 weeks, which in the presence of viral replication, favors the selection of resistant virus [22]. The rationale for the tail is to suppress viral replication until NVP plasma concentrations decrease to a level that will not promote the emergence of resistant virus. We hypothesized that increasing the duration or potency of the tail after SD-NVP therapy would decrease the incidence of NVP-resistant virus to <10% when measured with a sensitive assay.